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Related Experiment Videos

Cimetidine impairs nitrazepam clearance.

H R Ochs, D J Greenblatt, R Gugler

    Clinical Pharmacology and Therapeutics
    |August 1, 1983
    PubMed
    Summary
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    Cimetidine impairs the body's ability to process nitrazepam, a benzodiazepine. This drug interaction study found reduced nitrazepam clearance and longer elimination times when taken with cimetidine.

    Area of Science:

    • Pharmacology
    • Drug Metabolism
    • Clinical Pharmacology

    Background:

    • Cimetidine is known to inhibit drug oxidation.
    • Nitrazepam is a benzodiazepine derivative primarily metabolized by nitroreduction.

    Purpose of the Study:

    • To evaluate the effect of cimetidine on the hepatic clearance of nitrazepam in healthy subjects.
    • To determine if cimetidine alters nitrazepam absorption, distribution, or elimination.

    Main Methods:

    • Healthy subjects received oral nitrazepam doses with and without therapeutic cimetidine doses.
    • Nitrazepam serum concentrations were measured over 72 hours to determine pharmacokinetic parameters.
    • Key parameters assessed included absorption kinetics, volume of distribution, clearance, and elimination half-life.

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    Main Results:

    • Cimetidine did not affect nitrazepam absorption or volume of distribution.
    • Cimetidine significantly reduced nitrazepam clearance from 1.41 to 1.17 ml/min/kg.
    • The elimination half-life of nitrazepam was prolonged from 22.2 to 27.8 hours due to cimetidine treatment.

    Conclusions:

    • Cimetidine impairs the hepatic clearance of nitrazepam.
    • The findings suggest cimetidine's inhibitory effect on drug oxidation extends to nitroreduction pathways.
    • Clinicians should consider this interaction when prescribing nitrazepam concurrently with cimetidine.